Glaucoma is characterized by progressive atrophy of the optic nerve and is frequently associated with elevated intraocular pressure (IOP). The treatment of glaucoma has focused on the elevated IOP and only recently has the attention been shifted more to the optic nerve, where the disease process is predominantly seen. Effective treatment of glaucoma must somehow affect the conditions and metabolism of the optic nerve to stop the atrophic process.
Due to the inaccessibility of the optic nerve, its metabolism has not been thoroughly studied (Novak and Stefansson et al., Exp. Eye Res. 50, 289-96, 1990; and Clin. Exp. Ophthalmol 228, 128-33, 1990). A few reports exist on the blood flow in the optic nerve and retina and how this is affected by glaucoma drugs, such as carbonic anhydrase inhibitors. Vorstrup and associates (Vorstrup et al., J. Clin. Invest. 74: 1634-39 (1984)) found that intravenous administration of acetazolamide increased cerebral blood flow. The flow velocity in the intracranial arteries increased whereas a decrease was observed in the ophthalmic artery together with a decrease in ocular pulsatile blood flow (Kerty, et at, Acta Ophthalmol 73: 66-71 (1995) and Acta Ophthalmol 72: 401-8 (1994)), mainly originating from the choroidal circulation. In contrast, Rassam and associates (Rassam et al., Eye 7: 697-702 (1993)) found that intravenous acetazolamide increased retinal blood flow, whereas Grunwald et al., Invest Ophthalmol. Vis Sci 33: 504-7 (1992) found no effect by oral acetazolamide on macular blood flow evaluated with the blue field entopic technique; Harris and associates (Harris et al., Acta Ophthalmol 74: 569-72 (1996)) reported that the application of one drop of dorzolamide 3% decreased the artterio-venous transit time and increased the velocity of fluorescent particles in the paramacular and peripapillary microcirculations, whereas no effect was seen on flow velocity in the retrobulbar vessels.
Ischemia of the microcirculation around the papilla is assumed to be relevant for the pathogenesis of glaucomatous damage to the nerve fiber layer. Several drugs have been tested for their influence on perfusion of the posterior pole of the eye.
The present invention relates to the use of carbonic anhydrase inhibitors to increase vitreal oxygen tension over the optic nerve notwithstanding that oxygen is a powerful retinal vasoconstrictor of the retinal vessels (Hickman & Frayser, Circulation 33, 302-316 (1966)).